New tubulysin compound conjugates with polymers or biomolecules, having reduced toxicity compared with parent tubulysin, especially useful for treating tumor diseases

摘要

Conjugates (I) comprising tubulysins (natural cytotoxic tetrapeptides) or their analogs bonded to a polymer or biomolecule via a linker are new. Tubulysin compound conjugates of formula U-V-W (I) are new. U : tubulysin compound residue of formula (II); A : optionally substituted 5- or 6-membered heteroarylene; X : O, S, NR 1>3>or CR 1>4>R 1>5>; Y : O, S or NR 1>6>; R 1>-R 1>6>H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl; or two groups together form part of a cycloalkyl or heterocycloalkyl ring system; V : linker; and W : polymer or biomolecule. [Image] ACTIVITY : Cytostatic; Immunosuppressive; Antiinflammatory; Antirheumatic; Antiarthritic; Antidiabetic; Fungicide. MECHANISM OF ACTION : None given.